The adenovirus genome has recently been engineered to allow the insertion of foreign genes in a manner similar to that used to construct vaccinia recombinants. Expression of the inserted foreign gene(s) during adenovirus infection may induce the formation of antibodies capable of neutralizing the virus from which the foreign gene was obtained. We are testing this approach to develop recombinant rotavirus/adenovirus vaccines, hopefully more efficacious (more cross-reactive) and less reactogenic than the rhesus rotavirus vaccine. Current progress includes restriction mapping of the genome, cloning in plasmids of several restriction fragments corresponding to the E3 region and adjacent areas of the adenovirus 4 genome, and cloning of the NCDV rotavirus VP7 gene cDNA copy into a plasmid containing adenovirus 2 major late promoter cDNA. The right hand end of the adenovirus 4 genome (map units 83-100) has also been cloned. The VP7 glycoprotein gene of several human rotavirus strains and most of the fourth rotavirus gene from three different strains have been cloned in pBR322 or in the polylinker area of pUC vectors.